1. Field of the Invention
This invention relates to a novel carcinoma associated antigen (SK1) which is associated with various malignancies and monoclonal antibodies specific for epitopes on SK1.
2. Description of the Background Art
Murine monoclonal antibodies have been shown to mediate effective cytotoxicity to target cells in vitro; however, when utilized in vivo with humans, they have not achieved remarkable results. This is partially due to (i) the foreign nature of the injected murine proteins which leads to the development of a human anti-mouse antibody (HAMA) response, and (ii) the human effector functions which may not be fully activated by a murine antibody. In contrast, the dramatic effects which have been observed in systemically treating septic patients with purified human monoclonal or polyclonal antibodies (Ziegler, et al., The New England J. Med, 324:429-436, 1991; Kurtzberg, etal., Am. J. Pediatr. Hematol. Oncol., 9:299-301, 1987) and by intralesional therapy of melanoma suggests that the clinical use of human monoclonal antibodies (HuMAbs) (Irie, et al., Proc. Natl. Acad. Sci. USA, 83:8694-8698, 1986) will be successful. Thus, the potential use of human Mabs for cancer therapy is attractive.
Recent progress in the field of HuMAb technology has made it possible to generate numerous hybridomas of various specificities. Combined with knowledge gained in the understanding of the human immune response to cancer antigens (Lloyd, et al., Cancer Res., 49:3445-3451, 1989), several HuMAbs against tumor associated antigens (TAAs) have been produced and characterized. The reported tumor associated antigens recognized by HuMAbs include cell surface (Yoshikawa, et al., Jpn. J. Cancer Res. (Gann), 80:546-553, 1989; Yamaguchi, et al., Proc. Natl. Acad. Sci. USA, 84:2416-2420; Haspel, et al., Cancer Res., 45:3951-3961, 1985; Cote, et al., Proc. Natl. Acad. Sci. USA, 8-3:2959-2963, 1986; Glassy, Cancer Res., 47:5181-5188, 1987; and Borup-Christensen, et al., Cancer Detect. Prevent. Suppl., 1:207-215), cytoplasmic (Haspel, et al., Cancer Res., 45:3951-3961, 1985; Cote, et al., Proc. Natl. Acad. Sci. USA, 83:2959-2963, 1986; Glassy, Cancer Res., 47:5181-5188; Borup-Christensen, et al., Cancer Detect Prevent Suppl., 1:207-215, 1987; Kan-Mitchell, et al., Cancer Res., 49:4536-4541, 1989; and Yoshikawa, et al., Jpn. J. Cancer Res., 77:1122-1133, 1986), and nuclear antigens (McKnight, et al., Hum. Antibod. Hybridomas, 1:125-129, 1990).
At present, methods of limited effectiveness exist for treatment of various malignancies. Those drugs which are administered generally have severe side effects associated with their use. Accordingly, there exists a significant need to identify and purify an antigen associated with malignant diseases and to produce monoclonal antibodies which bind to epitopes on this antigen. Further, these antibodies are suitable agents for the diagnosis and treatment of malignancies expressing the SK1 antigen.